This study was conducted to determine the relationship between health fatalism and caregiver burden among caregivers of patients with MS. The study population consisted of 303 informal caregivers who provided care to patients with MS and presented to the Ondokuz Mayis University Health Practice and Research Center Neurology Clinic between September 2023 and August 2024. A descriptive information form developed by the researchers, the Health Fatalism Scale, and the Caregiver Burden Scale were used as data collection tools. Data were collected through face-to-face interviews. The data were analyzed with SPSS program, and p < 0.05 was considered statistically significant. The mean age of caregivers was 39.21 ± 12.02 years; 51.5
Anti-CD20 monoclonal antibodies are highly effective disease-modifying therapies for relapsing multiple sclerosis (RMS), but their comparative efficacy and safety versus teriflunomide, a dihydroorotate dehydrogenase inhibitor, remain clinically important. Teriflunomide is an oral platform treatment with moderate efficacy and a favorable administration profile, making it a relevant comparator for evaluating the benefit–risk profile of anti-CD20 therapies. To assess the efficacy and safety of anti-CD20 monoclonal antibodies compared with teriflunomide in adults with RMS. A systematic search of PubMed, Cochrane Library, Embase, ScienceDirect, and Scopus was conducted from inception to April 30, 2026. Randomized controlled trials (RCTs) and observational studies comparing anti-CD20 therapies with teriflunomide were eligible. Outcomes included annualized relapse rate, gadolinium-enhancing T1 lesions, new or enlarging T2 lesions, brain volume change, adverse events, serious adverse events, and infections. Pooled mean differences, rate ratios or risk ratios with 95
Exercise is increasingly recognized not only as a behavioral and preventive health intervention but also as a biologically active stimulus that may influence stress-responsive neural systems across molecular, autonomic, neurochemical, neuroimmune, and network levels. Evidence from human intervention studies, neuroimaging research, peripheral biomarker analyses, and preclinical models suggests that repeated physical activity may modulate pathways involved in emotional regulation, motivational processing, stress responsivity, interoceptive signaling, and adaptive neuroplasticity. However, the strength of evidence varies across mechanisms, and several cellular, receptor-level, and circuit-specific processes remain supported primarily by animal studies or indirect peripheral markers rather than direct causal demonstration in humans. This review synthesizes experimental, clinical, and conceptual evidence on exercise-induced neuroadaptation, with emphasis on neurochemical and neuropeptidergic mechanisms relevant to stress regulation and emotional disorders. We discuss exercise-associated adaptations involving dopaminergic, serotonergic, noradrenergic, glutamatergic, GABAergic, endocannabinoid, and opioid-related signaling, together with stress-responsive neuropeptides including corticotropin-releasing hormone, neuropeptide Y, oxytocin, orexin, β-endorphin, and substance P. Beyond isolated transmitter systems, we highlight interactions among hypothalamic peptidergic regulation, autonomic function, neurotrophic signaling, neuroimmune pathways, and large-scale neural network organization. We also introduce the biphasic neuroadaptation of the exercise framework, the neuroadaptive feedback loop of movement, and personalized neuromodulatory exercise profiling as heuristic models for organizing existing evidence rather than established clinical paradigms. Collectively, exercise may represent an emerging biologically informed neuromodulatory approach, although precision-based clinical application requires stronger causal human evidence, standardized biomarkers, and longitudinal validation.
Cardiac cephalalgia is a type of secondary headache that occurs in association with myocardial ischemia. It may present without typical chest pain, complicating early diagnosis and delaying optimal treatment. This study aims to evaluate the frequency of headache in a selected cohort of patients with myocardial infarction undergoing coronary angiography. We retrospectively reviewed 115 patients diagnosed with MI who underwent coronary angiography. The presence of headache prior to angiography was recorded, and follow-up was performed to assess its persistence after intervention. Statistical analyses included Chi-square, Mann-Whitney U and McNemar tests to evaluate associations between headache and clinical/laboratory parameters. A total of 90 patients were included in the study (mean age 57.8 years; 71 males). Among them, 27 patients (30
Takotsubo syndrome (TTS) is an acute stress-induced cardiomyopathy increasingly recognised as a disorder of the brain–heart axis. Neuroimaging studies have identified structural, functional and metabolic abnormalities within the central autonomic network, particularly the amygdala. Still, the role of amygdalar activity as a biomarker in TTS has not been systematically synthesised. A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251177487). PubMed, Web of Science, Cochrane Library, Google Scholar and ClinicalTrials.gov were searched through February 2025 for studies reporting neuroimaging findings in confirmed TTS. Data were extracted, narratively synthesised, and appraised against biomarker-qualification criteria. Directional consistency was additionally quantified by vote counting with exact binomial (sign) tests at the level of study–region–imaging domain, with Holm correction for multiplicity and sensitivity analyses excluding studies at high risk of bias. The search identified 489 records, of which 29 underwent full-text assessment; 10 studies met the inclusion criteria. Multimodal neuroimaging consistently implicated the amygdala, insula, hippocampus, thalamus, anterior cingulate and prefrontal cortex, with reduced amygdalar and insular grey matter, altered limbic structural connectivity, and disrupted central autonomic and default mode network connectivity. Two ¹⁸F-FDG PET/CT cohorts, the only included studies in which imaging preceded the outcome, found raised amygdalar metabolic activity before TTS onset that independently predicted subsequent syndrome development; the remaining eight were cross-sectional and cannot separate predisposition from consequence. Convergent, though directionally inconsistent, evidence supports a working model of chronic limbic sensitisation and exaggerated sympathoadrenal activation contributing to myocardial stunning. Vote counting confirmed that an abnormality was reported by almost every study assessing the amygdala (8/9), insula (6/6), prefrontal cortex (6/6) and hippocampus (5/5), but no region survived correction for multiplicity, and only the prefrontal cortex approached directional consistency (5/5 reduced; p = 0.062); amygdalar findings were directionally split (4 increased versus 3 decreased; p = 1.00). Excluding the two studies at high risk of bias altered no conclusion. Neuroimaging findings support TTS as a neurocardiac disorder characterised by dysfunction of limbic and autonomic brain networks. Amygdalar hyperactivity is the most frequently reported candidate marker of vulnerability, but none of these findings is clinically actionable, and the reasons are specific rather than generic: effect sizes are modest (Cohen’s d = 0.37–0.53), the direction of abnormality is inconsistent for every region except the prefrontal cortex, no included study reported test–retest reliability for its own primary measure, no study reported discrimination or calibration, and none tested incremental value over inexpensive psychometric or autonomic measures. These findings are therefore hypothesis-generating; adequately powered prospective cohorts and formal biomarker qualification are required before neuroimaging-guided risk stratification of the brain–heart axis can be considered for clinical use.
Cognitive impairment in multiple sclerosis (MS) is common but only weakly explained by conventional magnetic resonance imaging. Proton magnetic resonance spectroscopy (¹H-MRS) detects microstructural damage in normal-appearing white matter (NAWM). We examined whether regional NAWM metabolic profiles are spatially patterned in early relapsing–remitting MS (RRMS) and whether they relate to cognition. In this cross-sectional study, 52 patients with early RRMS (Expanded Disability Status Scale 0–3; 51 with usable spectroscopy) and 44 matched controls underwent multi-voxel three-dimensional ¹H-MRS at 3 tesla across six supracallosal NAWM regions. Group differences used Mann–Whitney tests with false discovery rate correction, and a group × region analysis tested for disease-related disruption. NAA/Cr–cognition associations used Spearman and partial correlations and multivariable models. NAA/Cr differed between groups in four of six regions, and a group × region interaction (p < 0.001) indicated that the regional NAA/Cr pattern in RRMS was disrupted beyond the physiological anterior–posterior gradient seen in controls. Frontal NAA/Cr correlated with processing speed (ρ = 0.350, p = 0.012) and parietal NAA/Cr with verbal learning (ρ = 0.327, p = 0.019), but neither survived adjustment for age or parsimonious modelling, in which disability was the main independent correlate of processing speed. Early RRMS shows spatially organised NAWM metabolic disruption. Regional NAA/Cr–cognition associations are detectable but weak and not independent of age or disability, and frontal NAWM integrity relates more to physical function than cognition, supporting a network-disconnection model with limited cognitive specificity. These findings are preliminary and need longitudinal confirmation.
Paroxysmal sympathetic hyperactivity (PSH) is a syndrome seen in a subgroup of survivors of severe acquired brain injury, most often traumatic, in which episodic surges of sympathetic activity occur together with motor over-activity, typically dystonic posturing. It is associated with longer intensive care stays, more complications, and worse outcomes, yet remains under-recognised. The difficulty is twofold: its core features overlap with the common emergencies of the intensive care unit, so that sepsis, seizures, pulmonary embolism, and drug-related syndromes are reasonably considered first; and no biomarker or imaging finding confirms it. This review offers a practical two-part approach for the patient with severe traumatic brain injury: how to recognise the syndrome positively, using the consensus definition and the PSH Assessment Measure, and how to differentiate it from its mimics. The differential is extended beyond the conditions usually listed to include autonomic dysreflexia, iatrogenic and substance withdrawal, endocrine emergencies, non-convulsive status epilepticus, unrelieved pain, and drug-induced autonomic instability, and the limitations of the evidence are examined rather than assumed. Attention is given to the pitfalls that cause delay and to the frequent coexistence of PSH with conditions such as sepsis. The evidence is drawn into a stepwise framework which has not been prospectively validated and is offered as an educational aid rather than a clinical guideline. Throughout, the emphasis falls on serial reassessment and dynamic reasoning, since substantial diagnostic uncertainty commonly persists.
Spastic cerebral palsy (CP) is characterized by impaired motor function, particularly in the lower limbs. Although both virtual reality (VR)-assisted gait training and proprioceptive neuromuscular facilitation (PNF) have demonstrated beneficial effects, evidence regarding their combined application remains limited. This exploratory study aimed to explore the effects of combined VR-assisted gait training and PNF on lower-limb motor function in children with spastic CP. Thirty children with spastic CP were randomly assigned to a conventional rehabilitation group (CG), a VR training group, or a combined VR and PNF group (PNF + VR), with 10 participants in each group. All participants underwent a 12-week intervention program. The primary outcomes were Gross Motor Function Measure-88 (GMFM-88) dimensions D (GMFM-88D) and E (GMFM-88E); secondary outcomes included the Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), lower-limb Fugl-Meyer Assessment (FMA), range of motion (ROM), and bone mineral density (BMD). A two-way mixed analysis of variance (ANOVA) was used to evaluate group-by-time interactions, with post hoc comparisons of change scores used as supportive analyses. All groups showed improvements in functional outcomes after the intervention. Significant group × time interaction effects were observed for GMFM-88D, MAS, FMA, and ROM (p < 0.05), with the PNF + VR group demonstrating the greatest improvements. Although GMFM-88E improved significantly in the PNF + VR group, as indicated by change-score comparisons, the interaction effect was not statistically significant. No significant interaction effects were found for BBS or BMD (p > 0.05). The combination of VR-assisted gait training and PNF may provide additional benefits in improving lower-limb motor function in children with spastic CP compared with conventional rehabilitation or VR training alone.
Alzheimer’s disease (AD) represents a profoundly detrimental neurodegenerative disorder, and early diagnosis coupled with effective treatment remains a major clinical challenge. MicroRNAs (miRNAs) have emerged as key regulators associated with pathological processes in AD. This study aimed to explore the expression pattern and the likely diagnostic value of miR-584-5p in AD, as well as its molecular mechanism of action in regulating β-amyloid (Aβ)-induced apoptosis. Peripheral blood samples from 90 AD patients and age- and sex-matched controls were examined using RT-qPCR. Correlation analyses of miR-584-5p expression with key AD biomarkers (Aβ42, tTau, pTau) were performed in AD patients. Following exposure to 5 µM Aβ1−42, SH-SY5Y cells were employed in subsequent functional experiments. Bioinformatics analysis, a dual-luciferase reporter assay, and negative correlation analysis of plasma samples were conducted to verify the target gene of miR-584-5p. miR-584-5p was significantly downregulated in AD patients, and its expression correlated with Aβ42 (r = 0.665), total tau (tTau, r = -0.642), phosphorylated tau (pTau, r = -0.576), and Mini-Mental State Examination (MMSE) scores (r = 0.618), yielding an AUC of 0.864 in this single-center cohort. miR-584-5p overexpression inhibited 5 µM Aβ1−42-induced apoptosis in SH-SY5Y cells, an effect that was reversed by concurrent HDAC1 overexpression. Mechanistically, by targeting HDAC1, miR-584-5p modulates p53 acetylation and the Bcl-2/Bax pathway at the protein level. miR-584-5p exerted neuroprotective effects via the miR-584-5p/HDAC1 axis, offering new insights into AD pathogenesis and suggesting this axis as a candidate for further preclinical investigation.
BACKGROUND:Motion sickness affects up to 30% of the general population, yet the three pharmacological agents currently approved in the United States, dimenhydrinate, meclizine, and scopolamine carry significant sedative and cognitive liabilities and offer incomplete protection against vomiting. Tradipitant, a selective neurokinin-1 receptor antagonist, has been evaluated across three randomized controlled trials for motion sickness prevention, but no pooled quantitative synthesis of this evidence exists. This study aimed to evaluate the efficacy and safety of tradipitant versus placebo in adults with a documented history of motion sickness. METHODS:PubMed, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov were searched from inception through March 25, 2026, following PRISMA guidelines (PROSPERO: CRD420261332049). Eligible studies were RCTs enrolling adults aged 18 years or older with documented motion sickness history. Binary outcomes were pooled as RRs using the Mantel-Haenszel method; continuous outcomes as MDs. Random-effects and fixed-effect models were applied to all outcomes. RESULTS:Three RCTs enrolling 808 participants were included, with two trials rated low risk of bias and one receiving some concerns. For vomiting incidence (primary outcome; 3 RCTs, n = 807), tradipitant significantly reduced vomiting risk versus placebo (RR 0.42, 95% CI 0.33 to 0.53; p-value < 0.0001; I² = 0%), with consistent dose-stratified estimates at 170 mg (n = 466; RR 0.38, 95% CI 0.28 to 0.53; p-value < 0.0001; I² = 0%) and 85 mg (n = 341; RR 0.46, 95% CI 0.32 to 0.65; p-value < 0.0001; I² = 0%), and a rough sea conditions pooled RR of 0.39 (95% CI 0.29 to 0.54). Nausea severity (3 RCTs, n = 491) showed no significant difference (SMD - 0.05, 95% CI - 0.24 to 0.13; p = 0.5846; I² = 0%; GRADE: Low). MSAQ total score (n = 488) was MD 1.43 (95% CI - 5.89 to 8.75; p = 0.4896; I² = 0%), MSAQ-GI subscale (n = 488) was MD - 3.14 (95% CI - 7.94 to 1.66; p = 0.1063; I² = 0%), and PGI-S score (n = 490) was MD - 0.18 (95% CI - 0.37 to 0.02; p = 0.0603; I² = 0%), none reaching significance. Any TEAE (n = 807) was significantly higher with tradipitant (RR 1.94, 95% CI 1.20 to 3.13; p = 0.0185; I² = 4.8%). However, individual adverse events did not reach significance: headache RR 1.45 (95% CI 0.85 to 2.50; p = 0.1283; I² = 0%), fatigue RR 2.23 (95% CI 0.78 to 6.36; p = 0.0940; I² = 0%), and somnolence RR 1.69 (95% CI 0.68 to 4.22; p = 0.1839; I² = 20.5%). CONCLUSION:Tradipitant significantly reduced vomiting incidence at both doses and across sea conditions, with negligible heterogeneity and stable sensitivity analyses. Although no significant improvement was observed in nausea or broader symptom burden, tradipitant was associated with a higher overall treatment-emergent adverse event rate than placebo. These findings support characterizing tradipitant as a selective vomiting prophylactic agent in the context of motion sickness; the absence of significant effects on nausea severity, MSAQ total and GI subscale scores, and PGI-S indicates that tradipitant should not be expected to provide comprehensive relief from the full symptomatic burden of motion sickness.
Prior studies have suggested an association between cervical artery dissection (CAD) and upper respiratory tract infection, although evidence remains scarce. We aimed to compare the clinical features and outcomes of CAD with and without history of upper respiratory infection. We conducted a secondary analysis of a multicenter, international, retrospective study including adult patients diagnosed with spontaneous CAD between January 2015 and June 2022. History of recent upper respiratory tract infection (HURI) was defined as symptoms of cough, fever, sneezing and throat soreness (at least two) within the 30 days preceding CAD diagnosis, as documented in patient medical records. Baseline characteristics and outcomes were compared between patients with and without HURI. Among 4,023 patients with CAD, 251 (6.2
Bell’s palsy is the most frequent reason for acute unilateral peripheral facial palsy. While some patients recover spontaneously, others experience incomplete recovery, asymmetry of face, synkinesis, disability, and decreased quality of life. The value of different rehabilitation paths in routine clinical practice is unknown. To describe facial recovery outcomes across three routine clinical rehabilitation pathways in adults with Bell’s palsy and to examine recovery patterns over 12 months. This single-center retrospective cohort study enrolled 500 adult patients with newly diagnosed Bell’s palsy and was conducted according to one of the three routine clinical pathways: no rehabilitation, rehabilitation with facial neuromuscular training, and neuromuscular training along with electrostimulation. The clinical evaluations were carried out at the moment of the initial clinical evaluation and then at 1 month, 3 months, 6 months, and 12 months after the index clinical evaluation. The primary outcome was favorable recovery within 6 months, which is considered as House-Brackmann grade I-II. The average age of participants was 45.3 years (SD 13.9 ) and 56.6
Spinal cord injury (SCI) is a devastating neurological condition characterized by pronounced neuroinflammation and progressive neurodegeneration. Matrix metalloproteinase-9 (MMP-9) has emerged as a crucial regulator of inflammatory cascades, yet its role as a predictive biomarker and enzyme kinetic behaviour persists ambiguous. MMP-9 has recently become a key and seemingly distinct contributor to brain physiology and pathology. The local and time-constrained nature of MMP-9 actions may be the reason why it is so specific, even when it is released into the brain by cells of different types, such as neurons, glia, and leukocytes. The aims of the study were to examine the enzymatic kinetics of MMP-9 in acute spinal cord injury, determine how MMP-9-inhibitor-I inhibits MMP-9, and correlate MMP-9 levels with the severity of injury and neuroinflammatory indicators to explore the inhibitory response of MMP-9 inhibitor-I in vitro and evaluate the potential relevance of MMP-9 as a severity-associated biomarker and experimental inhibitory target in acute SCI. In this cross-sectional study, 160 patients with confirmed acute SCI were stratified according to the American Spinal Injury Association Impairment Scale into Mild/Moderate and severe groups. Serum concentrations of MMP-9, C-reactive protein (CRP), creatine kinase-BB (CK-BB), and routine biochemical markers were quantified. Multivariable regression analyses were performed to adjust for confounding variables, and receiver operating characteristic (ROC) curve analysis was used to assess the discriminatory performance of MMP-9. MMP-9 levels were significantly elevated in patients with severe SCI compared with Mild/Moderate injury (p < 0.001) and showed a strong positive correlation with injury severity (r = 0.755, p < 0.001) and positive correlation with CK-BB levels (r = 0.223, p = 0.047). MMP-9 remained independently associated with SCI severity in the adjusted model. ROC analysis demonstrated excellent discriminatory performance (AUC = 0.942; 95
